The digestive system iscomposed by the gastrointestinal track (GI), accessory glands and organs. Thegastrointestinal tract is a tube that runs from mouth to rectum and it isdivided into seven parts: mouth, pharynx, esophagus, stomach, small and largeintestine, and rectum. The purpose of the GI track is to conduct, and digestfood into absorbable units that the body can use as energy; it does so byperforming four basic processes to the food we ingest: motility, secretion,digestion and absorption (Sherwood, 2016). The GI track’s wall consists of themucosa, submucosa, muscularis externa and serosa layers. The mucosa is theinnermost layer of the GI track and its main function is to absorb nutrients.
Ontop of the mucosa layer is the submucosa, which is a layer of connective tissuethat contains blood vessels and provides support and elasticity to the GItrack; it also contains the submucosal plexus, which is composed of severalnerves. The muscularis externa layer is composed of two layers of smooth musclelayers: the inner layer is circular and contracts inwards, while the outerlayer is longitudinal and contracts in length (makes it shorter); these layersprovides motility to the GI track. When combining the movement of both circularand longitudinal smooth muscle, segmentation and peristalsis occur. Segmentationis a circular movement which allows mixing of the bolus, and peristalsis is thelongitudinal movement which pushes the bolus forward (Sherwood, 2016). Theoutermost layer of the GI track wall is the serosa which prevents friction withorgans surrounding the GI track. In this lab, we focused on the small intestineand its muscularis externa layer of smooth muscle.
Thesmooth muscle found in the GI track wall has several anatomical andphysiological properties, which combined, give rise to intestinal motility. Smoothmuscle is not striated, meaning it does not have z lines and it is notorganized into sarcomeres; instead, it has dense bodies and intermediatefilaments. In addition, smooth muscle does not contain t-tubules and has apoorly developed sarcoplasmic reticulum with little calcium (SR); its activity requiresthe influx of extracellular calcium (Sherwood, 2016). Smooth muscle cells areactivated by calcium dependent phosphorylation of myosin (Clinton, 2003). Thereare two types of smooth muscle: multiunit, smooth muscle cells innervated independentlyby neurons for small movements, and unitary, where there is a collection ofthem innervated by one neuron. Unitary smooth muscle is found in the GI track.Also, smooth muscle has gap junctions which allow the propagation of electricalactivity. Smooth muscle receives inputs from the autonomic central nervoussystem (ACS), and the enteric nervous system (ENS), these two have differentnerves which contact multiple parts of smooth muscle cells (Sherwood, 2016).
TheGI’s smooth muscle has its own peacemaking activity; its pacemaker cells.called interstitial cells of Cajal (ICC), have a slower rate than the pacemakercells of the heart; about 12 cycles per minute (Sherwood, 2016). ICC create slowwaves, or also called Basal electric rhythm (BER), which depend on the openingand closing of calcium channels and calcium-dependent potassium channels. Whencalcium gated channels open, there is an extracellular calcium influx into thecell’s cytosol, calcium concentration increases inside the cell and this leadsto an action potential spike (Kito et al, 2015). Once the concentration ofcalcium inside the cell is high enough, calcium induces the opening ofpotassium channels, and potassium causes the hyperpolarization of the cell. Thencalcium channels close and calcium concentration inside the cell decreases. Theclosing of calcium-dependent-potassium channels is necessary before anotheraction potential spike takes place.
There are two sources of calcium in smoothmuscle: extracellular, and from the sarcoplasmic reticulum (SR). In response a stimulus,voltage gated channels in caveoli open and allow the influx of extracellularcalcium following its concentration gradient; this calcium binds to calmodulin(Ca-CAM). Ca-CAM activates MLC kinase which phosphorylates myosin, and leads tocontraction (Sherwood, 2016). Muscle relaxation occurs when intracellularcalcium levels decrease and MLC phosphatase activity increases (Clinton, 2003).
Calcium release from the SR occurs by calcium-induced-calcium releasesmechanism or by IP3 activation of the SR calcium channels. The later mechanisminvolves the binding of an agonist, into the G-protein complex which activatesphospholipase C and causes IP2 to become IP3; IP3 then binds to SR receptorswhich causes calcium channels in SR to open, leading to calcium efflux (Nowak, 1985). The ACS also influencesthe activity of the smooth muscle of the GI tract wall. The sympathetic nervoussystem suppresses the GI system, while the parasympathetic, through the vagusnerve, stimulates it (Sherwood, 2016). The sympathetic nervous system’sneurotransmitter is typically norepinephrine, an adrenergic agent, which stimulatesadrenergic receptors. The stimulation of these receptors activates adenylcyclase and activates MLC phosphatase, which dephosphorylates myosin, leading toa decrease of cross-binding and muscle tension.
On the other hand,parasympathetic activity relies on the cholinergic agent acetylcholine, whichstimulates muscularis receptors activating phospholipase C. These cause thedepolarization of IP2 to IP3 which activate MLC kinase; myosin then isphosphorylated and increases cross-binding activity (Nowak, 1985). Tension inthe smooth muscle increases. Frequency of contraction is not affected by eitherparasympathetic nor sympathetic activity. Inthis lab we measured the motility of the intestinal segment while being treatedwith different substances: epinephrine, methacholine, Adenosine-5’diphosphate(ADP) and Ca2+-free Ringer-Tyrode’s solution. The purpose of this lab was toobserve and examine the effect these substances have on the motility of thesmall intestinal segment, and what effect does an environment with no calciumhas on smooth muscle. We measured three parameters to compare activity of “baseline”(control) and “with-substance” motility: tension, frequency and wave amplitude.
We expected to see the following results on each trial: In trial 1, if we treatthe intestinal segment with epinephrine, an adrenergic agent, we expect to seea decrease in tension and wave amplitude, but no effect in frequency. In trial2, if we apply methacholine, a cholinergic agent, to the intestinal segment, weexpected an increase in tension and wave amplitude, and no change in frequency.In trial 3, if the segment is treated with ADP, a purinergic agent, we expectto see a decrease in tension and wave amplitude and no effect on frequency. Lastly,if we submerge the intestinal segment into Ca2+-free Ringer-Tyrode’s solution,we expected to see a decrease in tension, amplitude and frequency.